Currently, biologic drugs account for more than half of all therapeutic drug candidates in pharmaceutical development pipelines. These biologic drugs need to be delivered through the parenteral route. As the parenteral therapeutic drugs become more and more popular, portable automatic medication injection or infusion devices for self-administration are expected to be widely used together with the parenteral therapeutic drugs (also referred as combination products). In clinical trials, using the automatic medication injection or infusion devices can have apparent advantages over using manual syringe. For example, when using manual syringe, the manual injection force difference between the low concentration formulation (or placebo) and the high concentration formulation can be sensed by user, and therefore, the blinding effect for clinical trial will be diminished. In contrast, the user won't feel this difference if using the automatic medication injection or infusion devices because the injection/infusion forces of these devices are provided by device internal driving mechanisms. Meantime, these automatic drug delivery devices often can deliver drug more precisely than manual device.
Clinical trials of new drugs provide critical data on the drug's effectiveness, dosage requirements and possible adverse side effects. Unlike marketing strategies developed and applied to the introduction and sales of a new drug, it is desired and sometimes necessary in clinical studies to conceal or “blind” the drug to be studied. Blinding the clinical study is believed necessary to prevent bias from the participants—patients, investigators and sponsors—from comprising the results. Blinded studies can also enhance marketability of a product by more credibly demonstrating the favorable health and economic advantages, such as greater therapeutic efficacy and fewer adverse effects, when compared with a marketed drug or placebo. In addition, many governments require blinded clinical studies for approval of a new drug. (See 21 C.F.R. 314.26 and European Union's Directive 91/507/EEC). Effective blinding requires each aspect of the treatment—dosage form, packaging, labeling, dosage interval, dosage strength and dosage composition—to appear the same. That is, none of the participants to the study should be able to discern whether they are taking placebo, one or more strengths of investigational drug, or one or more strengths of comparator drug (the comparator or control drug is a marketed drug commonly used for the disease being studied). The blinding procedure is further complicated by the need to comply with all aspects of Good Manufacturing Practices (GMP) requirements.
Autoinjector or infusor devices, as the most used automatic drug delivery devices for self-administering parenteral therapeutic drugs, are mostly designed for fix dose delivery. This presents following challenge to be used for clinical trial: difficult to conduct clinical trial when different doses are evaluated, for example, during the dose-finding clinical study. This challenge often delays the introduction of autoinjector or infusor device to clinical trial until the final dose is determined. Clinical trial is the most time consuming and most expensive part of drug development. Normally, all the three phases clinical trial together can take 5-8 years and cost hundreds of million dollars. During the long time period and with the substantial spending, there are a lot of learning about the drug, for example, how the drug is absorbed, metabolized, and what the drug effect look like. On the other hand, when the parenteral therapeutic drug is developed together with the drug delivery device, there isn't much learning about the delivery device in the early phases of clinical trial, especially human factor and usability of the device, which is highly recommended by Food and Drug Administration (FDA) (FDA draft guidance—Applying Human Factors and Usability Engineering to Optimize Medical Device Design, 2011). As mentioned above, in phase I and phase II clinical trials, a very important aspect is dose-finding, which requires devices that can deliver variable dose. Therefore, the current fixed dose drug delivery device is often introduced during very late stage of clinical trial. In contrast, for oral drugs, the dose forms are being optimized throughout the all phases of the clinical trial period. Currently, the clinical trial for parenteral therapeutic drug start with vial/manual syringe combination. Until phase III, the more sophisticated device, such as autoinjector or infusor will be introduced and studied. Or, the more sophisticated device will be evaluated after the first launch of the drug in vial/manual syringe format. As the results, drug developers not only under-utilize the advantage of using autoinjector or infusor device in clinical trials, but also lose the opportunity to test device human factors and usabilities during the clinical trials.
In summary, what is needed is a new method for conducting blinded clinical studies which permits for improved development of parenteral therapeutic products with automatic drug delivery device during clinical trials.